Discovery of Hits That Can Specifically Inhibit Necroptosis but Not Apoptosis

Necroptosis or programmed necrosis is a specialized and regulated necrosis, and is unmasked when apoptotic machinery for death stress is defective. Initially, it was proposed that necroptotic cell death was pathologically associated with ischemic brain injury and retinal disorders. In contrast, it plays a beneficial significance in innate immune response to viral infection that can evade host’s apoptotic surveillance. Also, it has been therapeutically emerging as the strategy to overcome the cancers with acquired anticancer drug resistance. Presently, a few small molecules to interfere with signaling pathways for necroptosis have been disclosed since necrostatin-1 (Nec-1) was for the first time identified as an inhibitor of receptor interacting protein 1 (RIP1), a key necroptosis regulator. In an effort to discover hits that can selectively inhibit necroptotic cell death, in this study, we screened in-house and in silico chemical libraries in a cell-based format. Eventually, 7 hits were identified from in-house chemical library while 2 hits were from computer modeling. Most hits less protected cells from tumor necrosis factor alpha (TNFα)- and zVAD-mediated necroptosis than a reference compound necrostatin-1, without affecting apoptotic cell death induced in HeLa. Interestingly, a few of hits had preferential protective effects on zVAD or TNFα while Nec-1 exhibited EC50 values at the similar concentrations against both necroptosis inducers, suggesting that chemicals deduced in our study can discriminate signaling pathways leading to receptor or nonreceptor-mediated necroptotic cell death.Therefore, some potent hits will be further improved to use for the treatment of necroptosis-associated disorders. &nbsp

Effects of Music Therapy on Patients with Cancer Receiving Outpatient Treatment

Patients with cancer often experience anxiety when waiting for diagnostic test results, before receiving treatment, or when informed of a recurrence. Therefore, appropriate interventions are required at each of these stages. This study determines the effects of music therapy with preferred music on anxiety, blood pressure, pulse, and the satisfaction of patients with cancer when receiving outpatient intravenous therapy in a long-term care facility. This quasi-experimental non-equivalent control-group and non-synchronized study was conducted in the outpatient injection room of a long-term care facility in South Korea. This study included 57 patients (divided into experimental and control groups) with female reproductive system/breast or digestive system cancer who received short-term intravenous vitamin C on an outpatient basis. The participants chose from a music selection table for each genre, which was based on the prior research, under the supervision of a professor experienced in music therapy. The participants selected 20 songs to listen to for 1 h while receiving intravenous therapy. The participants were surveyed for state anxiety and satisfaction to confirm the effects of music therapy, and their systolic and diastolic blood pressure and pulse were measured. The state anxiety (U=282, p=.046) and satisfaction (U=262, p=.016) scores of the experimental and control groups revealed significant differences. There were no significant differences in systolic blood pressure (U=311, p=.13), diastolic blood pressure (t=1.88, p=.065), and pulse (t=-0.5, p=.61) between the experimental and control groups. Music therapy is an effective intervention for reducing anxiety and improving satisfaction in patients with cancer when receiving short-term outpatient treatment. However, to generalize these results, a larger sample size of participants is needed with similar types of cancer

Effects of LGBT Nursing Education Using Simulation

PURPOSE: As health care needs for Lesbian, Gay, Bisexual and Transgender (LGBT) are becoming increasingly important, it has become imperative for the nurses to be attentive towards their health problems and provide nursing care with an open-minded attitude. Due to limited opportunity to provide direct nursing care to LGBT patients, it is hypothesized that simulation would provide good opportunity for students to experience LGBT nursing care in a safe environment. This study was conducted to develop and apply simulation of LGBT nursing care to ultimately provide unbiased nursing care for LGBT population and prepare basic data for LGBT nursing education. METHODS: This study was a single-group pre-post experimental design study for 57 senior nursing students based on the comparison of existing LGBT knowledge, general attitude towards LGBT, and nursing attitude towards LGBT before and after simulation. The scenario content included discussion of coming out issue, providing sexual health information, and supportive nursing care for LGBT population. Data were analyzed with descriptive statistics and Wilcoxon signed rank. RESULTS: Simulation education-led to a significant increase in LGBT knowledge and nursing attitude. However, there was no change in the general attitude towards LGBT. CONCLUSION: The results of this study suggest that LGBT education using simulation may be effective for nursing students and nurses from the point of concern for LGBT population. It is hypothesized that future LGBT educational programs might need more detailed information from both care recipients and nurses. Finally, LGBT education needs to be included in the nursing education curriculum

Monitoring of multi-frequency polarization of gamma-ray bright AGNs

We started two observing programs with the Korean VLBI Network (KVN) monitoring changes in the flux density and polarization of relativistic jets in gamma-ray bright AGNs simultaneously at 22, 43, 86, 129 GHz. One is a single-dish weekly-observing program in dual polarization with KVN 21-m diameter radio telescopes beginning in 2011 May. The other is a VLBI monthly-observing program with the three-element VLBI network at an angular resolution range of 1.0--9.2 mas beginning in 2012 December. The monitoring observations aim to study correlation of variability in gamma-ray with that in radio flux density and polarization of relativistic jets when they flare up. These observations enable us to study the origin of the gamma-ray flares of AGNs.Comment: 4 pages, 4 figures, Proceedings of the conference "The innermost regions of relativistic jets and their magnetic fields", Granada, Spai

Analytical Model for Deflections of Bonded Posttensioned Concrete Slabs

This paper presents a finite element analysis approach to evaluate the flexural behavior of posttensioned two-way slabs depending on the tendon layout. A finite element model was established based on layered and degenerated shell elements. Nonlinearities of the materials are considered using the stress-strain relationships for concrete, reinforcing steel, and prestressing tendons. Flexural testing of the posttensioned two-way slabs was conducted to validate the developed analytical process. Comparing the analytical results with the experimental results in terms of deflections, it showed generally good agreements. Also a parametric study was performed to investigate the effects of different types of tendon layout

Inhibition of c-Jun NH(2)-terminal kinase or extracellular signal-regulated kinase improves lung injury

BACKGROUND: Although in vitro studies have determined that the activation of mitogen-activated protein (MAP) kinases is crucial to the activation of transcription factors and regulation of the production of proinflammatory mediators, the roles of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in acute lung injury have not been elucidated. METHODS: Saline or lipopolysaccharide (LPS, 6 mg/kg of body weight) was administered intratracheally with a 1-hour pretreatment with SP600125 (a JNK inhibitor; 30 mg/kg, IO), or PD98059 (an MEK/ERK inhibitor; 30 mg/kg, IO). Rats were sacrificed 4 hours after LPS treatment. RESULTS: SP600125 or PD98059 inhibited LPS-induced phosphorylation of JNK and ERK, total protein and LDH activity in BAL fluid, and neutrophil influx into the lungs. In addition, these MAP kinase inhibitors substantially reduced LPS-induced production of inflammatory mediators, such as CINC, MMP-9, and nitric oxide. Inhibition of JNK correlated with suppression of NF-κB activation through downregulation of phosphorylation and degradation of IκB-α, while ERK inhibition only slightly influenced the NF-κB pathway. CONCLUSION: JNK and ERK play pivotal roles in LPS-induced acute lung injury. Therefore, inhibition of JNK or ERK activity has potential as an effective therapeutic strategy in interventions of inflammatory cascade-associated lung injury

KIOM-4 Protects against Oxidative Stress-Induced Mitochondrial Damage in Pancreatic β-cells via Its Antioxidant Effects

The protective effect of KIOM-4, a mixture of plant extracts, was examined against streptozotocin (STZ)-induced mitochondrial oxidative stress in rat pancreatic β-cells (RINm5F). KIOM-4 scavenged superoxide and hydroxyl radicals generated by xanthine/xanthine oxidase and Fenton reaction (FeSO4/H2O2), respectively, in a cell-free chemical system. In addition, a marked increase in mitochondrial reactive oxygen species (ROS) was observed in STZ-induced diabetic cells; this increase was attenuated by KIOM-4 treatment. Mitochondrial manganese superoxide dismutase (Mn SOD) activity and protein expression were down-regulated by STZ treatment and up-regulated by KIOM-4 treatment. In addition, NF-E2 related factor 2 (Nrf2), a transcription factor for Mn SOD, was up-regulated by KIOM-4. KIOM-4 prevented STZ-induced mitochondrial lipid peroxidation, protein carbonyl and DNA modification. Moreover, KIOM-4 treatment restored the loss of mitochondrial membrane potential (Δψ) that was induced by STZ treatment, and inhibited the translocation of cytochrome c from the mitochondria to the cytosol. In addition, KIOM-4 treatment elevated the level of ATP, succinate dehydrogenase activity and insulin level, which were reduced by STZ treatment. These results suggest that KIOM-4 exhibits a protective effect through its antioxidant effect and the attenuation of mitochondrial dysfunction in STZ-induced diabetic cells